The NIH's HEAL Initiative aims to support collaboration between clinical research experts in academia and industry to accelerate the development of highly efficacious, non-addictive analgesics for well-defined chronic pain syndromes. The University of Rochester (UR), and its proposed leadership for the UR Hub and Spokes within Early Phase Pain Investigation Clinical Network (EPPIC-Net), have extensive expertise in designing and conducting analgesic trials of small molecule drugs, devices, and biologics. These trials have included both investigator-initiated phase 2 trials and participation multi-site industry-sponsored clinical trials with a main focus on well-phenotyped chronic low back pain (CLBP) syndromes, which is one of the top priorities for the NIH's proposed EPPIC-Net. Currently, there are thirteen committed potential protocol PIs at the UR Hub and four Spokes. Together these PIs have the ability to recruit subjects with a broad range of pain conditions from the following subspecialties: anesthesiology, dentistry, emergency medicine, gastroenterology, gynecology, neurology, neurosurgery, oncology, orthopedics, pediatrics, rheumatology, and urology. Each of these committed potential PIs has extensive clinical trial experience and existing infrastructure to support patient recruitment and retention, timely and accurate data entry, and regulatory documentation. In addition, the proposed UR-EPPIC-Net Collaboration Core is well equipped to recruit additional Spoke sites using the members' broad, regional and national network of analgesic researchers. UR has multiple resources to promote efficient subject recruitment and trial quality, including (1) the UR Clinical and Translational Science Institute's Trial Hub Liaison Team and Recruitment Unit, Community Engagement Studios, and Clinical Research Center; (2) the Practice-Based Research Network of regional primary care practices; and (3) the Office for Human Subject Protection ? Quality improvement division. The UR also has multiple resources to support deep phenotyping of chronic pain patients, including (1) the Neuroimaging Core, (2) the Neuromuscular Pathology Laboratory, (3) quantitative sensory testing expertise, and (4) the Physical Exercise Activity Kinesiology Laboratory. This proposal outlines a leadership and oversight infrastructure to allow for the nimble, efficient, and high integrity implementation of EPPIC-Net clinical trials. Institutional leadership commitments include the use of a central Institutional Review Board (IRB) and the adoption and implementation of master trial agreements templates. As a result, the proposed UR-EPPIC-Net Hub and Spokes are well positioned to work with the EPPIC-Net Data and Clinical Coordination Centers to design and rapidly conduct phase II therapeutic trials across a broad range of pain conditions, and to set new standards for conception, implementation, and dissemination of pain research.